Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

Tomas Kalincik*, Timothy Spelman, Maria Trojano, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, Alessandra Lugaresi, Raymond Hupperts, Edgardo Cristiano, Vincent Van Pesch, Francois Grand'Maison, Daniele Spitaleri, Maria Edite Rio, Sholmo Flechter, Celia Oreja-Guevara, Giorgio Giuliani, Aldo Savino, Maria Pia Amato, Thor Petersen, Ricardo Fernandez-BolanosRoberto Bergamaschi, Gerardo Iuliano, Cavit Boz, Jeannette Lechner-Scott, Norma Deri, Orla Gray, Freek Verheul, Marcela Fiol, Michael Barnett, Erik Van Munster, Vetere Santiago, Fraser Moore, Mark Slee, Maria Laura Saladino, Raed Alroughani, Cameron Shaw, Krisztian Kasa, Tatjana Petkovska-Boskova, Leontien Den Braber-Moerland, Joab Chapman, Eli Skromne, Joseph Herbert, Dieter Poehlau, Merrilee Needham, Elizabeth Alejandra Bacile Bacile, Walter Oleschko Arruda, Mark Paine, Bhim Singhal, Steve Vucic, Jose Antonio Cabrera-Gomez, Helmut Butzkueven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.

METHODS: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.

RESULTS: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.

CONCLUSIONS: Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

Original languageEnglish
Article numbere63480
JournalPLOS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 2013

Keywords

  • Adult
  • Demography
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interferon beta-1a
  • Interferon-beta
  • Kaplan-Meier Estimate
  • Likelihood Functions
  • Magnetic Resonance Imaging
  • Male
  • Medication Adherence
  • Multiple Sclerosis
  • Propensity Score
  • Reproducibility of Results
  • Treatment Outcome
  • Withholding Treatment
  • Clinical Trial
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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